<3,3-2H2>-1-phenyl-1,3-propanediol | 73738-29-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: <3,3-2H2>-1-phenyl-1,3-propanediol
• 英文别名: 1,1-dideuterio-3-phenylpropane-1,3-diol
• CAS: 73738-29-1
• 化学式: C₉H₁₂O₂
• 分子量: 154.177
• InChiKey: RRVFYOSEKOTFOG-RJSZUWSASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  11.0
• 可旋转键数：
  3.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  40.46
• 氢给体数：
  2.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  <3,3-2H2>-1-phenyl-1,3-propanediol 在 氢氧化钾 、 dipotassium peroxodisulfate 、 adogen 464 、 potassium ruthenate 、 对甲苯磺酸 作用下， 以 二氯甲烷 、 苯 为溶剂， 反应 8.0h， 生成 vinyl-d2 phenyl ketone
  参考文献：
  名称：

  Stereoselective ring opening of 1-phenylcyclopropylamine catalyzed by monoamine oxidase-B

  摘要：

  The inactivation of monoamine oxidase (MAO) by 1-phenylcyclopropylamine (1-PCPA, 1) has been proposed (Silverman, R. B.; Zieske, P. A. Biochemistry 1985,24,2128-2138) to proceed via a radical mechanism involving ring opening of an unstable cyclopropylaminyl radical (Scheme I). This intermediate has been shown to partition between attachment to the N-5 position of the covalently-bound flavin cofactor, which results in irreversible inactivation, and attachment to an active-site cysteine residue, which results in an unstable adduct that hydrolyzes to release acrylophenone and active enzyme over time. The stereochemistry and mechanism of the ring-opening step is investigated in this paper. The enantiomerically pure dideuterated 1-PCPA analogues 5 and 6 were prepared and used to inactivate MAO. Extractions of the acrylophenone metabolites released on decomposition of the reversible cysteine adducts that were formed during inactivation by 5 and by 6 were subjected to GCMS analysis. It was found that the inactivation by the R-isomer (5) produced 66% of [beta,beta-H-2(2)]acrylophenone, 19% of [alpha-H-2]acrylophenone, and 15% of unlabeled acrylophenone; inactivation by the S-isomer (6) resulted in formation of 4% of [beta,beta-H-2(2)]acrylophenone, 6% of [alpha-H-2]-acrylophenone, and 90% of unlabeled acrylophenone. These results are indicative of a stereoselective ring opening, preferentially forming beta,beta-dideutero adduct 8 following inactivation by 5 (Scheme II) and the alpha,alpha-dideuterio adduct 13 following inactivation by 6 (Scheme III). Stereoselective exchange of a single a deuterium on adduct 13 is proposed to account for the complete washout of deuterium in the product and the observed deuterium isotope effect of 3.1 on the reactivation of 6-inactivated MAO. The difference in the amount of cleavage of the two cyclopropyl bonds with each enantiomer may be due, at least in part, to a secondary deuterium isotope effect on the formation of the dideuterated carbon radical. This secondary deuterium isotope effect also provides a rationalization that favors a mechanism involving electron transfer to the aminium radical cation followed by cyclopropyl ring cleavage and then combination with an active-site cysteine radical. The results do not support a direct S(H)2 mechanism. The preference for cleavage of one of the cyclopropane bonds is believed to be the result of asymmetry at the active site which is set up for stereospecific removal of the pro-R proton from substrates; the pro-R C-H bond of substrates corresponds to the cyclopropane bond in 1-PCPA that is preferentially broken.

  DOI：

  10.1021/ja00065a002
• 作为产物：
  描述：

  β-羟基苯丙酸乙酯 在 lithium aluminium deuteride 作用下， 以 乙醚 为溶剂， 以60%的产率得到<3,3-2H2>-1-phenyl-1,3-propanediol
  参考文献：
  名称：

  Stereoselective ring opening of 1-phenylcyclopropylamine catalyzed by monoamine oxidase-B

  摘要：

  The inactivation of monoamine oxidase (MAO) by 1-phenylcyclopropylamine (1-PCPA, 1) has been proposed (Silverman, R. B.; Zieske, P. A. Biochemistry 1985,24,2128-2138) to proceed via a radical mechanism involving ring opening of an unstable cyclopropylaminyl radical (Scheme I). This intermediate has been shown to partition between attachment to the N-5 position of the covalently-bound flavin cofactor, which results in irreversible inactivation, and attachment to an active-site cysteine residue, which results in an unstable adduct that hydrolyzes to release acrylophenone and active enzyme over time. The stereochemistry and mechanism of the ring-opening step is investigated in this paper. The enantiomerically pure dideuterated 1-PCPA analogues 5 and 6 were prepared and used to inactivate MAO. Extractions of the acrylophenone metabolites released on decomposition of the reversible cysteine adducts that were formed during inactivation by 5 and by 6 were subjected to GCMS analysis. It was found that the inactivation by the R-isomer (5) produced 66% of [beta,beta-H-2(2)]acrylophenone, 19% of [alpha-H-2]acrylophenone, and 15% of unlabeled acrylophenone; inactivation by the S-isomer (6) resulted in formation of 4% of [beta,beta-H-2(2)]acrylophenone, 6% of [alpha-H-2]-acrylophenone, and 90% of unlabeled acrylophenone. These results are indicative of a stereoselective ring opening, preferentially forming beta,beta-dideutero adduct 8 following inactivation by 5 (Scheme II) and the alpha,alpha-dideuterio adduct 13 following inactivation by 6 (Scheme III). Stereoselective exchange of a single a deuterium on adduct 13 is proposed to account for the complete washout of deuterium in the product and the observed deuterium isotope effect of 3.1 on the reactivation of 6-inactivated MAO. The difference in the amount of cleavage of the two cyclopropyl bonds with each enantiomer may be due, at least in part, to a secondary deuterium isotope effect on the formation of the dideuterated carbon radical. This secondary deuterium isotope effect also provides a rationalization that favors a mechanism involving electron transfer to the aminium radical cation followed by cyclopropyl ring cleavage and then combination with an active-site cysteine radical. The results do not support a direct S(H)2 mechanism. The preference for cleavage of one of the cyclopropane bonds is believed to be the result of asymmetry at the active site which is set up for stereospecific removal of the pro-R proton from substrates; the pro-R C-H bond of substrates corresponds to the cyclopropane bond in 1-PCPA that is preferentially broken.

  DOI：

  10.1021/ja00065a002

文献信息

• SCHAAL C.; RICARD M., J. LABELLED COMPOUNDS AND RADIOPHARM., 1979, 16 NO 5 727-733
  作者：SCHAAL C.、 RICARD M.

  DOI：——

  日期：——